This is the Phase I application of a SBIR project that will be devoted to develop a new fecal DNA test for CRC screening, which will utilize a new tri-marker panel discovered in our preliminary study. CRC is the second deadliest cancer in USA. The good news is that early detection along with resection is associated with a five-year survival rate of nearly 100%. Fecal DNA testing is emerging as one of the most promising methods to replace fecal occult blood tests for CRC screening. Recently, we discovered a new panel of stool DNA markers that could detect 86% of CRC with a specificity of 82%. Because this new panel contains no methylated DNA markers, a great benefit of using it for CRC screening is that the quantity of the stool used to extract DNA could be reduced by at least 10 fold, greatly reducing the complexity and cost of fecal DNA testing. To the best of our knowledge, this may be the simplest panel of markers that can achieve such high detection sensitivity with good specificity. The specific aim of this Phase I project is to validate this new marker panel for CRC screening. The validation will be carried out using the training-test set procedure. The milestone set for Phase I is to demonstrate that the new marker panel can detect ~85% of CRC with a specificity of ~80%.